The overarching purpose of this proposal is to address a set of critical questions about the etiology of interstitial cystitis (IC) using multivariate data from a large population-based classical twin study. Despite ongoing research, IC remains a controversial entity for two critical reasons. First, the validity of the case definition remains uncertain. There are few data that address a historically important validator--the degree to which IC results from genetic and/or environmental factors. Second, IC is often comorbid with one or more additional physical disorders and yet the causes of comorbidity are uncertain. Taken together, these two sets of unanswered questions contribute significantly to the controversies that continue to surround IC. Moreover, the strong female predominance of IC has been amply documented but is not well understood. To address these fundamental issues, we propose to conduct a twin study of IC in the population-based Swedish Twin Registry (STR). We propose to assess IC in the cohort of STR twins aged 18-45 years using a web-based screening instrument. Those not participating in the web-based assessment will be offered a computer assisted telephone interview. Based on previous experience, we anticipate that of the 50,011 individuals in this cohort, 75% or 37,500 will respond. These unique data will be used to address the following Specific Aims: (1) To estimate the prevalence of IC and its key co-morbidities in STR participants. To assess the phenotypic patterns of comorbidity of IC with other disorders. (2) To evaluate the genetic and environmental sources of variation for IC through concordances and structural equation modeling. To examine the effects of gender on these effects. (3) To use multivariate twin analyses to investigate the sources of covariation between IC and its frequently co-morbid conditions and (4) To use case-control designs with external controls and internal controls ("co-twin control" design) to evaluate the importance of exposures which may infer risk for disease.